Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
PLoS One. 2011;6(11):e27365. doi: 10.1371/journal.pone.0027365. Epub 2011 Nov 15.
Defects in the cilium, a once thought vestigial organelle, have recently been implicated in many human diseases, including a number of cystic kidney diseases such as polycystic kidney disease (PKD), Bardet Bieldl Syndrome, and Meckel-Gruber Syndrome. In a forward genetic screen, qilin was identified as a novel gene important in the pathogenesis of kidney cysts in zebrafish. In this paper we characterized qilin(hi3959A) mutant's phenotypes in detail, investigated cilia formation in this mutant and performed structural and functional analysis of the Qilin protein. Results reveal Qilin's essential role in cilia assembly and maintenance in multiple organs, including the kidney, the lateral line organ, and the outer segment of the photoreceptor cell. In addition, rescue experiments suggest that defective pronephric cilia correlate with the formation of kidney cysts in qilin(hi3959A) mutants. Further, genetic analysis suggests that qilin interacts with multiple intraflagellar transport (IFT) complex B genes, which is supported by the striking phenotypic similarities between qilin(hi3959A) and IFT complex B mutants. Finally, through deletion analysis we provide evidence that the well-conserved N-terminus and the coiled-coil domain of Qilin are both essential and sufficient for its function. Taken all the observations together, we propose that Qilin acts in a similar role as IFT complex B proteins in cilia assembly, maintenance and kidney development in zebrafish.
纤毛是一种曾经被认为是退化的细胞器，最近其缺陷与许多人类疾病有关，包括多种囊性肾病，如多囊肾病（PKD）、Bardet-Biedl 综合征和 Meckel-Gruber 综合征。在正向遗传学筛选中，麒麟被鉴定为斑马鱼肾脏囊肿发病机制中的一个新的重要基因。在本文中，我们详细描述了 qilin(hi3959A)突变体的表型，研究了该突变体中纤毛的形成，并对 Qilin 蛋白进行了结构和功能分析。结果表明，Qilin 在包括肾脏、侧线器官和光感受器细胞外节在内的多个器官的纤毛组装和维持中发挥着重要作用。此外，挽救实验表明，缺陷的肾前体细胞纤毛与 qilin(hi3959A)突变体中肾脏囊肿的形成有关。此外，遗传分析表明，麒麟与多个内鞭毛运输（IFT）复合物 B 基因相互作用，这与 qilin(hi3959A)和 IFT 复合物 B 突变体之间惊人的表型相似性相支持。最后，通过缺失分析，我们提供了证据表明，Qilin 的保守 N 端和卷曲螺旋结构域对于其功能都是必需和充分的。综上所述，我们提出 Qilin 在斑马鱼纤毛组装、维持和肾脏发育中与 IFT 复合物 B 蛋白发挥类似的作用。
